tbuckley/cabot-search huggingface dataset:
QOL-26. Exploring the experience of young people receiving remotely delivered Acceptance and Commitment Therapy following treatment for a brain tumour
Authors: Katie Powers, Jac Airdrie, Sophie Thomas, Faith Gibson, Chloe Geagan, Nic Davies, Sam Malins
Journal: Neuro-Oncology (2022)

Abstract Despite high survival rates of children and young people diagnosed with a brain tumour, survival is often associated with poor psychological, physical, and social outcomes. Acceptance and Commitment Therapy (ACT) is an evidence-based psychological intervention shown to improve psychological and physical outcomes in adults and children with chronic disease, including cancer. The ACT Now study investigates the feasibility of ACT delivered remotely with young people who have experienced a brain tumour. This study aims to describe participant experience whilst better understanding the impact of therapy and capturing the barriers and facilitators to engagement. Participants of the ACT Now study were invited to take part in a semi-structured interview with questions covering experience of study initiation, receipt of ACT, remote delivery and overall impact of ACT. Ten participants who had previously undergone treatment for a brain tumour have been interviewed to date. Interviews were transcribed verbatim and coded into broad themes. We found that pre-therapy mood and altruism served as motivation for interviewees’ involvement in the study. Interviewees reported hoping to learn coping techniques to navigate fluctuating moods and the pressures of young adult life. Despite the technology used for remote delivery occasionally malfunctioning, interviewees reported increased ability to access therapy via this method. However, an overall preference for face-to-face therapy delivery was reported with interviewees describing that they felt communication might have been easier in person. The therapeutic relationship and the therapists’ flexible schedules were seen as facilitators to session attendance. Barriers to attendance were scarcely reported but included scheduling conflicts due to work or school. ACT was highly regarded amongst interviewees and provided an opportunity for them to learn about themselves and how they can live in accordance with their personal values. Interviewees benefitted from ACT psychologically, physically, and socially and reported an overall positive experience of study involvement.
LVEF decline in relation to body composition among women treated for breast cancer: WF-97415.
Authors: Kerryn Reding, Nathaniel S. O'Connell, Richard Cheng, Johnny Nguyen, Amy Ladd, Jennifer Jordan, Bonnie Ky, Alexi Vasbinder, Vlad Zaha, Alexander Lucas, Tonya Calhoun, Mary Helen Hackney, Moriah Bellissimo, Ralph D'Agostino, Glenn Jay Lesser, W. Gregory Hundley
Journal: Journal of Clinical Oncology (2022)

10556 Background: Despite an improvement in survival from breast cancer (BC), many women experience cardiotoxicity. Left ventricular ejection fraction (LVEF) is reduced by an average of 9.7% in women receiving anthracyclines. Obesity and central adiposity at BC diagnosis may influence risk of LVEF decline. We sought to examine associations between body composition and LVEF decline in the UPBEAT (Understanding and Predicting Fatigue, Cardiovascular Decline, and Events After Breast Cancer: WF-97415) study, which was conducted in collaboration with NCI Community Oncology Research Program. Methods: The analytic cohort was comprised of 167 women treated for stage I-III BC with chemotherapy and/or radiation in the UPBEAT prospective study, in whom LVEF was obtained at baseline (pre-treatment) and 3 months. Linear regression was used to examine LVEF decline in relation to 1) waist circumference (WC) and body mass index (BMI) at baseline and 2) changes in WC and BMI during BC treatment. All models were adjusted for age and race. Results: In this cohort (mean [SD] age: 55.7 [10.8] yrs; in whom 75% were white; 19% were Black), the mean (SD) LVEF at baseline was 60.7 (6.7)% with a mean decline of 2.7 (7.2)% from baseline to 3-months. Both WC and BMI at BC diagnosis were associated with LVEF decline during follow-up (Table). For each additional inch in WC, EF decreased by 0.25% points at 3 months (P=0.024); for each additional kg/m 2 in BMI, EF decreased by 0.2% points at 3 months (P=0.007). Reduced BMI during treatment was associated with LVEF decline, whereas a change in WC was not. Each kg/m 2 reduction in BMI was associated with a 0.4% point decrease in LVEF (p=0.037). Anthracycline use was associated with a 1.89% point decline in LVEF at 3 months versus non-users (p=0.049). After additional adjustment for anthracycline use, baseline WC remained statistically significantly associated with LVEF decline to the same degree. Conclusions: These data show that central adiposity at BC diagnosis is associated with LVEF decline during treatment, even after controlling for anthracyclines. Loss of central adiposity was not associated with LVEF decline, whereas BMI loss during treatment was. This suggests that shifts in body composition during BC treatment, potentially via loss of muscle mass, are important to monitor in patients. Future work should examine how changes in body composition, particularly changes in skeletal muscle and adipose tissue depots, influence cardiac dysfunction in BC patients during treatment. Funding: 2UG1CA189824, R01CA199167, 2UG1CA189828. [Table: see text]
The expression of androgen receptor splice variant 7 at radical prostatectomy predicts the risk of progression in untreated non-metastatic prostate cancer patients
Authors: M. Maggi, A. Sciarra, S. Salciccia, A. Nicolai, E. Tortorella, S. Giantulli, F.M. Magliocca, I. Silvestri, L. Taglieri, S. Cattarino, S. Scarpa
Journal: European Urology (2022)
ICON3D technology: The intraoperative display for hyper-accuracy 3D models in laparoscopic partial nephrectomy
Authors: D. Amparore, F. Piramide, A. Pecoraro, P. Verri, E. Checcucci, S. De Cillis, A. Piana, G. Volpi, S. Granato, M. Sica, A. Bellin, G. Cattaneo, M. Manfredi, C. Fiori, F. Porpiglia
Journal: European Urology (2022)
Complementary and alternative medicine exposure in oncology (CAMEO) study: A multi-institutional cross-sectional analysis of patients receiving cancer treatment.
Authors: Ryan J. Hutten, Christopher R. Weil, Brandon M. Barney, Angela Fagerlin, David K. Gaffney, David Michael Gill, Gary Whipple, Terence Duane Rhodes, Laura Scherer, Gita Suneja, Jonathan David Tward, Theresa Louise Werner, Jaden Evans, Skyler B Johnson
Journal: Journal of Clinical Oncology (2022)

e18739 Background: Compared to standard of care treatments, complementary and alternative medicine (CAM) use has been associated with decreased survival in cancer patients. CAM includes a broad range of treatments including vitamins/minerals, herbs/supplements, special diets, and mind/body interventions. An improved understanding of contemporary prevalence, predictors and intended goals of CAM use is needed to improve the cancer patient experience and guide shared decision-making regarding risks and benefits of their use. Methods: A cross-sectional survey of prospectively enrolled adult cancer patients treated at a large regional non-profit cancer center and an NCI-Designated Comprehensive Cancer Center between 2020 and 2021 was collected. Patients receiving cancer treatment were selected for analysis and grouped based on reported CAM use. Differences between CAM users and nonusers were assessed by chi-squared for categorical and two-sample t-test for continuous variables. Predictors of CAM use were identified with univariable and multivariable logistic regression. Results: Of 749 respondents, 83.31% had heard of or been recommended a CAM. Rates of CAM use during cancer treatment were highest for vitamins/minerals (56%), mind/body (52%), herbs/supplements (38%), special diets (30%), and other (12%). In the most common primary cancers, overall rates of CAM use were high (Breast: 84%, prostate: 66%, lung: 79%). Most patients (91%) use CAM in addition to conventional treatments. The intended goal of CAM therapy was most often management of symptoms (42%), treatment of cancer (30%), and mental health (15%). CAM users were younger than non-users (median age 62 years [y] vs 65y, p = 0.03). Females had higher rates of CAM use compared to males (86% vs. 78%, p &lt; 0.01). Patients with incurable cancer had higher rates of CAM use than those with curable cancer (82% vs. 72%, p &lt; 0.01). Predictors of CAM use on multivariable model include female gender (OR 2.5, p &lt; 0.01) and incurable cancer (OR 2.5, p &lt; 0.01). During cancer treatment, patients using CAM used multiple therapies and therapy types, including an average of 3.3 vitamins/minerals, 3.1 herbs/supplements, 2.5 mind/body exercises, and 1.6 special diets. Conclusions: CAM use is common among cancer patients receiving radiation, chemotherapy, and or surgery. Many patients are taking multiple CAM therapies during treatment with one third of patients using CAM with the intended goal of treating their cancer. This data provides details about and predictors of CAM use and provides information to guide patient-physician discussions.
GCT-06. Management of a congenital intracranial teratoma: a case report and review of literature
Authors: Margaret Shatara, Evan Cantor, Kristie N Ramos, Jonathan Yu, Ahmad Hassan, Joshua S Shimony, Peng Cheng Han, Ashley Meyer, Andrea Ogle, Michele McHugh, Tammy Green, Mary Beck, Andrew Cluster, Nicole Brossier, Joshua Rubin, Sonika Dahiya, Mohamed S Abdelbaki, Jennifer Strahle
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Congenital intracranial teratomas (CITs) are rare tumors occurring in the first 60 days of life, often associated with dismal prognosis, posing challenges in both oncologic and surgical management. METHODS: We report a patient with a congenital mature teratoma diagnosed prenatally, who underwent successful surgical resection following neoadjuvant chemotherapy. We also performed an updated literature review on CIT outcomes. RESULTS: A newborn female, diagnosed prenatally with a complex midline intracranial echogenic mass, underwent postnatal brain MRI which demonstrated a supratentorial large complex enhancing mass with solid and cystic components, with associated obstructed hydrocephalus. Serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin were normal for age. Tumor biopsy revealed mature teratoma. AFP obtained from cyst fluid during fenestration was significantly elevated at 8 weeks of life. Due to concerns for possible malignant transformation and in an attempt to alter tumor vascularity facilitating surgical resection, the patient received two cycles of neoadjuvant carboplatin and etoposide, followed by tumor resection without significant intraoperative bleeding. There was no evidence of immature components on final pathology. The patient remains without tumor recurrence, now 9 months, since surgical resection. Review of literature yielded 76 cases of CITs: eight patients with mature teratoma, of which six remained alive following tumor resection. Five patients with immature teratoma received chemotherapy prior to resection; three remained alive post-resection (follow-up range 3-20 years). DISCUSSION: CITs are typically associated with poor prognosis, with reported one-year survival of 7.2-12%. Surgical excision is the mainstay of treatment, often limited by intraoperative hemorrhage. Neoadjuvant chemotherapy has been employed as a successful strategy to reduce tumor volume and vascularity in a variety of pediatric brain tumors; more specifically, carboplatin and etoposide are utilized as neoadjuvant chemotherapy for non-germinomatous germ cell tumors to facilitate excision in older children. Their role in CITs requires further evaluation.
Metformin: Is it a drug for all reasons and diseases?
Authors: Chris R. Triggle, Ibrahim Mohammed, Khalifa Bshesh, Isra Marei, Kevin Ye, Hong Ding, Ross MacDonald, Morley D. Hollenberg, Michael A. Hill
Journal: Metabolism (2022)

Metformin was first used to treat type 2 diabetes in the late 1950s and in 2022 remains the first-choice drug used daily by approximately 150 million people. An accumulation of positive pre-clinical and clinical data has stimulated interest in re-purposing metformin to treat a variety of diseases including COVID-19. In polycystic ovary syndrome metformin improves insulin sensitivity. In type 1 diabetes metformin may help reduce the insulin dose. Meta-analysis and data from pre-clinical and clinical studies link metformin to a reduction in the incidence of cancer. Clinical trials, including MILES (Metformin In Longevity Study), and TAME (Targeting Aging with Metformin), have been designed to determine if metformin can offset aging and extend lifespan. Pre-clinical and clinical data suggest that metformin, via suppression of pro-inflammatory pathways, protection of mitochondria and vascular function, and direct actions on neuronal stem cells, may protect against neurodegenerative diseases. Metformin has also been studied for its anti-bacterial, -viral, -malaria efficacy. Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an anti-hyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct anti-viral actions. Clarification is also sought as to whether data from ex vivo studies based on the use of high concentrations of metformin can be translated into clinical benefits, or whether they reflect a 'Paracelsus' effect. The environmental impact of metformin, a drug with no known metabolites, is another emerging issue that has been linked to endocrine disruption in fish, and extensive use in T2D has also raised concerns over effects on human reproduction. The objectives for this review are to: 1) evaluate the putative mechanism(s) of action of metformin; 2) analyze the controversial evidence for metformin's effectiveness in the treatment of diseases other than type 2 diabetes; 3) assess the reproducibility of the data, and finally 4) reach an informed conclusion as to whether metformin is a drug for all diseases and reasons. We conclude that the primary clinical benefits of metformin result from its insulin-sensitizing and antihyperglycaemic effects that secondarily contribute to a reduced risk of a number of diseases and thereby enhancing healthspan. However, benefits like improving vascular endothelial function that are independent of effects on glucose homeostasis add to metformin's therapeutic actions.
SIK2 inhibition enhances PARP inhibitor activity synergistically in ovarian and triple-negative breast cancers
Authors: Zhen Lu, Weiqun Mao, Hailing Yang, Janice M. Santiago-O’Farrill, Philip J. Rask, Jayanta Mondal, Hu Chen, Cristina Ivan, Xiuping Liu, Chang-Gong Liu, Yuanxin Xi, Kenta Masuda, Eli M. Carrami, Meng Chen, Yitao Tang, Lan Pang, David S. Lakomy, George A. Calin, Han Liang, Ahmed A. Ahmed, Hariprasad Vankayalapati, Robert C. Bast
Journal: Journal of Clinical Investigation (2022)

Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) have had an increasing role in the treatment of ovarian and breast cancers. PARP inhibitors are selectively active in cells with homologous recombination DNA repair deficiency caused by mutations in BRCA1/2 and other DNA repair pathway genes. Cancers with homologous recombination DNA repair proficiency respond poorly to PARP inhibitors. Cancers that initially respond to PARP inhibitors eventually develop drug resistance. We have identified salt-inducible kinase 2 (SIK2) inhibitors, ARN3236 and ARN3261, which decreased DNA double-strand break (DSB) repair functions and produced synthetic lethality with multiple PARP inhibitors in both homologous recombination DNA repair deficiency and proficiency cancer cells. SIK2 is required for centrosome splitting and PI3K activation and regulates cancer cell proliferation, metastasis, and sensitivity to chemotherapy. Here, we showed that SIK2 inhibitors sensitized ovarian and triple-negative breast cancer (TNBC) cells and xenografts to PARP inhibitors. SIK2 inhibitors decreased PARP enzyme activity and phosphorylation of class-IIa histone deacetylases (HDAC4/5/7). Furthermore, SIK2 inhibitors abolished class-IIa HDAC4/5/7-associated transcriptional activity of myocyte enhancer factor-2D (MEF2D), decreasing MEF2D binding to regulatory regions with high chromatin accessibility in FANCD2, EXO1, and XRCC4 genes, resulting in repression of their functions in the DNA DSB repair pathway. The combination of PARP inhibitors and SIK2 inhibitors provides a therapeutic strategy to enhance PARP inhibitor sensitivity for ovarian cancer and TNBC.
EPEN-20. PDL1 expression and tumor-infiltrating immune cell subpopulations: The role of immune-checkpoint molecules in the prognosis of patients with supratentorial ependymoma and its correlation to survival
Authors: Rafat Malik, Agrima Sharma, Amandeep Kumar, Manmohan Singh, Vaishali Suri, Mehar Chand Sharma
Journal: Neuro-Oncology (2022)

Abstract Immune checkpoint blockade of the programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has shifted the way advanced cancers are treated. The 'ST-RELA fusion positive' and 'PF-A' molecular subgroups of ependymomas (EPN) have a dismal prognosis. AIMS: This study is undertaken to look for immunological microenvironment in ependymomas. Based on L1CAM protein expression and/or the presence of RELA/YAP1 fusion transcripts by RT-PCR, all supratentorial (ST) Grade-II/III EPNs were classified as ST-RELA, ST-YAP, and ST-not otherwise specified (NOS). Based on H3K27me3 protein expression and chromosome 1q gain, all posterior fossa (PF) EPNs were classified as PF-A or PF-B. PD-L1 (SP263, Ventana) and CD8 immunohistochemistry was performed. The enrichment of RelA protein at the PDL1 promoter site was investigated using chromatin immunoprecipitation-qPCR (ChIP-qPCR) in three ST-RELA samples. A total of 83 intracranial EPNs were included in our preliminary data, and we discovered that PD-L1 expression correlates with increasing cytotoxic T-lymphocyte infiltrates in intracranial ependymomas using PD-L1 and CD8 IHC. The majority of PD-L1-positive intracranial EPNs are members of the ST-RELA subset, which also has the highest CTL density. Our findings suggest that ST-RELA EPNs could be used in immunotherapy to target immune checkpoint modulators. To further this research, we are looking into the presence of tumour infiltrating cells such as CD3, CD8, CD163, FOXP3, and others, which can aid in characterising the tumour microenvironment in cell types expressing PD-L1.This study will also be used to predict the prognostic significance of PD-L1/PD1 and other tumour cell infiltrating biomarkers in ependymomas and correlate it with survival outcomes.
Factors associated with dose adjustment for the bortezomib, lenalidomide, dexamethasone regimen among patients with newly diagnosed multiple myeloma.
Authors: Tao Ran, Rohan Medhekar, Alex Z. Fu, Sharmila Patel, Shuchita Kaila
Journal: Journal of Clinical Oncology (2022)

8039 Background: VRd (bortezomib/lenalidomide/dexamethasone) has become one of the established treatment regimens in the US for multiple myeloma (MM). Due to toxicities, dose adjustments are often required for VRd. This real-world study described the patient characteristics and factors associated with dose adjustment among MM patients treated with VRd as first line (1L) therapy. Methods: Adult MM patients treated with 1L VRd were selected from the Optum Clinformatics database (Nov 1, 2015-Sep 30, 2020). Patient characteristics were evaluated during a 6-month baseline period. Dose adjustments were defined based on lenalidomide (len) dose received during 1L. Receipt of &gt; 15mg len was categorized as VRd regular, ≤15mg len as VRd lite, and initial len dose &gt; 15mg reduced to ≤15 mg over treatment period as VRd reduced. Baseline factors associated with different VRd dose categories were studied using multinomial logistic regression. Results: Among the 1497 patients identified, the mean (SD) age was 69 (9.5) years (52% ≥70), 51% were male, 59% were White, 37% were frail, and 67% with Medicare. Baseline Charlson Comorbidity Index was 4.2, with hypertension (70%), hyperlipidemia (56%), renal impairment (26%), and CVD (25%) being the most prevalent comorbidities. Over half of the patients received an adjusted dose, VRd lite (33%) and VRd reduced (22%). Overall, for patients treated with 1L VRd, median follow-up was 16.2 months; median duration of 1L was 4.9 months (among those with confirmed end of therapy); and median TTNT was 14.5 months. Compared to VRd regular, use of VRd lite was over 6 times more likely to be associated with patients ≥75 years of age, about 2 times more likely to be associated with females, and about 40% less likely to be associated with commercial insurance vs. Medicare; VRd reduced was 1.3 times more likely to be associated with females, and 1.5 times more likely to be associated with frail patients (table). No differences were observed among different races. Conclusions: Over half of the MM patients treated with 1L VRd in the real-world were &gt; 70 years of age and over one-third were frail. A large proportion of patients received a modified dose of VRd. Receipt of VRd lite dose was highly associated with older age (≥75 years), and receipt of VRd reduced dose was associated with frailty. These dose adjustments may potentially result in reduced efficacy of the VRd regimen in the real-world relative to controlled clinical trials, which needs to be assessed in future studies. [Table: see text]
Stochasticity in threshold of homologous recombination deficiency (HRD) score.
Authors: Bai Xu, Bai Xu, Zhentian Kai, Phuong Anh Nguyen Thi, Chaoran Xia, Weiwei Shi
Journal: Journal of Clinical Oncology (2022)

e17561 Background: HRD test from Myriad Inc. was approved by FDA as a biomarker for niraparib in ovarian cancer. Its threshold (as 42) was initially established by capturing 95% of tumors with BRCA1/2 mutation and BRCA1 promoter methylation in the training cohort. Here, we explored the stochasticity of such threshold, when the test noises themselves were concerned. Methods: We simulated HRD scores from figure 1 of Telli et al., 2016 by assigning the median from each histogram bin to the associated samples. The threshold was calculated, as described in the original paper, and the standard error (SE) and confidence interval (CI) for such threshold were estimated from bootstrapping the cohort. Furthermore, the entire cohort was down-sampled to determine the effect of sample size on the threshold. Results: The threshold of 42.5 was calculated from our simulated dataset, close to the original one, with SE of 1.62 and 95% CI of 40.75 - 47.5 for the bootstrap. As expected, SE steadily increased to 2.21, 2.84, 2.97 when the sample sizes decreased to 250, 230, and 210 respectively. When the dataset was further down-sampled to include only 200 BRCA deficient samples, SE increased to 3.76, and drastically, CI ranged between 36.5 and 51.2. Conclusions: We have showed there exists manifest stochasticity in the original threshold of 42 for the Myriad HRD test, which is likely close to platform noise in magnitude. The minimum size of BRCA deficient patients to obtain a stable threshold is 200, as shown in our study.